Objective: To obtain useful information concerning the mechanisms by which certain polycyclic aromatic hydrocarbons cause stable alterations in gene expression leading to changes in growth control and other phenotypic abnormalities in cells in culture. Approach: The approaches being used in this project may be listed as follows: (1) The development and characterization of a cloned cell culture model system of mouse embryo cells for use in subsequent studies. (2) The detection and characterization of carcinogen binding sites (receptors) in the cytosol. (3) The determination of carcinogen binding to nuclear subfractions and macromolecular components of chromatin. (4) The identification of the actual compounds bound to chromatin and an examination of the biologic activity of the compounds extracted from chromatin. (5) Characterization of chemically transformed and non-transformed populations of cloned cells with respect to chromatin composition, chromatin template capacity for RNA-dependent RNA synthesis, and endogenous RNA polymerases. (6) An examination of the acute effects caused by the chemical carcinogens, noncarcinogenic polycyclic hydrocarbons and pyrimidine analogs (virus activators) on nuclear acidic protein synthesis and degradation, chromatin template capacity, and nuclear endogenous RNA polymerase activities. (7) An examination of the effects of carcinogen metabolism on intracellular macromolecular binding and induced alterations in transcriptional events.